کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1926372 1536452 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A study of human furin specificity using synthetic peptides derived from natural substrates, and effects of potassium ions
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
A study of human furin specificity using synthetic peptides derived from natural substrates, and effects of potassium ions
چکیده انگلیسی

We explored furin substrate requirements in addition to the motif R-X-K/R-R using synthetic fluorescent resonance energy transfer (FRET) decapeptides. These decapeptides were derived from furin cleavage sites in viral coat glycoproteins and human and bacterial protein precursors. The hydrolysis by furin of most substrate was activated by K+ ion, whereas kosmotropic anions of the Hofmeister series were inhibitors. The analysis of furin hydrolytic activity showed that its efficiency is highly dependent on the particular combinations of amino acids at different substrate positions. There is a clear interdependence of furin subsites that must be taken in account in determining its specificity and also for the design of inhibitors. However, clear preferences were detected for substrates with S at P1′, and V at P2′, at P3′ the amino acids D, S, L and A are almost equally frequent. In the non-prime subsites the best substrates presented S and H at P6; basic amino acids at P5; and no clear tendency at P3. Interestingly, two amino acid substitutions on the prime side of the peptide derived from H5N1 influenza hemagglutinin furin processing site highly improved its hydrolysis. These modifications are possible by single point mutations, suggesting a potential yield of a more infectious virus.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 487, Issue 2, 15 July 2009, Pages 105–114
نویسندگان
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